This invention relates to hygroscopic carriers and compositions, foamable carriers, and foamable pharmaceutical and cosmetic compositions, and the use of them.
External topical administration is an important route for the administration of drugs in disease treatment. Many groups of drugs, including, for example, antibiotic, anti-fungal, anti-inflammatory, anesthetic, analgesic, anti-allergic, corticosteroid, retinoid and anti-proliferative medications are preferably administered in hydrophobic media, namely ointment. However, ointments often form an impermeable barrier, so that metabolic products and excreta from the wounds to which they are applied are not easily removed or drained away. Furthermore, it is difficult for the active drug dissolved in the carrier to pass through the white petrolatum barrier layer into the wound tissue, so the efficacy of the drug is reduced. In addition, ointments and creams often do not create an environment for promoting respiration of the wound tissue and it is not favorable to the normal respiration of the skin. An additional disadvantage of petroleum jelly-based products relates to the greasy feeling left following their topical application onto the skin, mucosal membranes and wounds.
Foams and, in particular, foams that are substantially based on non-aqueous solvents are complicated systems which do not form under all circumstances.
There remains an unmet need for improved, easy to use, stable and non-irritating foam formulations, intended for treatment of dermal and mucosal tissues. Particularly, there remains an unmet need for improved, easy to use, stable and non-irritating foam formulations, with unique therapeutic properties. There is more particularly a need to develop hygroscopic carriers and compositions, foamable carriers and foamable compositions and foams with active agents, which are stable, are non irritating, that facilitate penetration at a target, that are presentable in an easily applicable stable form, that can be handled with ease thereby facilitating compliance and that are adaptable where there is a need to minimize the amount of free water and in consequence, the potential breakdown of ingredients/agents by oxidation/hydrolysis.
Some active agents are known to be generally unstable or susceptible to isomerization or to breakdown, resulting in loss of activity and the use of stabilizers, anti oxidants antimicrobials and buffers and the like in aqueous compositions to protect active or cosmetic agents is known. The problems of protecting active pharmaceutical and cosmetic agents in waterless environments, such as polar compositions are multifold and can vary according to the type of waterless environment and the nature of the agent being used. It has been surprisingly found that factors like small levels of acid residues in the raw materials can be significant in influencing agent stability. Similarly, the presence of low levels of metal ions can act to catalyze reactions or breakdown. There is therefore a need for simple and elegant solutions to stabilize active ingredients in a waterless or substantially waterless environment. On one level it is far from simple or obvious to produce waterless foamable compositions that, when released, produce foams of quality suitable for pharmaceutical or cosmetic application. On a further level having realized a carrier that will produce a waterless foam of quality there is an additional difficulty to be overcome, namely how to adapt the formula and achieve a formulation, which can accept a range of various active pharmaceutical and cosmetic agents such that the composition and active agent are stable and the foam produced remains of quality. Specifically, one of the challenges in preparing such waterless or substantially waterless foamable compositions is ensuring that the active pharmaceutical or therapeutic agent does not react, isomerizes or otherwise break down to any significant extent during its storage and use. Particularly, there remains an unmet need for improved, easy to use, stable and non-irritating foam formulations, with unique therapeutic or beneficial properties containing a stable or stabilized active pharmaceutical or cosmetic agent.
Polyethylene glycol or derivatives or mixtures thereof and propylene glycol or derivatives are believed, in addition to their function as a solvent, to support, facilitate, improve or optimize the function and effect of active agents and may themselves have a therapeutic effect. There is thus, also an unmet need for compositions especially foamable compositions comprising combinations of polyethylene glycols or derivatives or mixtures thereof and polyethylene glycol or derivatives with an active agent, especially synergistic compositions.